Psychiatric diseases are devastating and poorly understood. The goal of this project is to [unreadable] identify the cell biological phenotypes that underlie autism and other psychiatric[unreadable] disorders, taking advantage of new developments in human stem cell technology. I[unreadable] propose to harvest skin fibroblasts from patients with autism, to reprogram these cells to[unreadable] generate induced pluripotent stem (iPS) cells, and to differentiate the iPS cells into[unreadable] neurons. I will then use a set of semi-automated in vitro assays to develop a phenotypic[unreadable] fingerprint for each cell line focusing on the developmental and functional phenotypes[unreadable] that are likely to lead to autism. We will use automated microscopes, cell sorters and[unreadable] semi-automated patch clamps to measure the differentiation, migration, survival,[unreadable] morphology, and excitability of neurons derived from patients. Finally, we will take[unreadable] advantage of the genetic information available for some autistic patients to determine[unreadable] whether deletion, duplication, or mutation of specific genes leads the phenotypes[unreadable] observed in the neurons from that patient. This approach has the potential to[unreadable] revolutionize our study of autism and other psychiatric disorders. It will allow us to link[unreadable] the phenotype and genotype of patients with the cell biological defects that give rise to[unreadable] disease. In addition, it will allow us to develop cell-based assays to both investigate the[unreadable] etiology of the disease and to find new treatments for these untreatable disorders.